The underlying hypothesis of this proposal is that inhibitors of ganglioside biosynthesis will prevent or slow the growth of neural crest-derived tumors (neuroblastoma, melanoma, astrocytoma). These tumor types produce an altered array of gangliosides that contribute to their growth and spread. Genetic and pharmacological experiments have proven that gangliosides are good targets for the treatment of neuroblastoma and melanoma. The current inhibitors of ganglioside biosynthesis have shown efficacy in mouse cancer models; however, these compounds act by inhibiting all glycosphingolipids (GSLs). Gangliosides are only a small subset of GSLs. The broad GSL inhibition mediated by the current inhibitors causes side effects; therefore, a ganglioside specific inhibitor should be superior. Here, we propose to develop a system to identify ganglioside specific inhibitors. These inhibitors should reduce the side effects of non-specific GSL inhibition while maintaining efficacy as anti-cancer agents. The goal of this proposal is to develop a system to discover drugs that block the production of gangliosides. Gangliosides are cell surface carbohydrates that are required for certain types of cancer such as melanoma and neuroblastoma. Using the system described here, new drugs can be discovered which will lead to new treatments for patients with melanoma or neuroblastoma. [unreadable] [unreadable] [unreadable]